Incident rate ratios (IRR) for treatment A-1210477 in vivo discontinuation were
higher with two generic formulations compared to the proprietary product (IRR, 1.3; 95% CI 1.04–1.63). Adherence (medication possession ratio, >80%) was higher (IRR, 1.19; 95% CI 1.11–1.27) and the new use of gastric medications (3.4–4.9%) lower with branded than with the generic equivalent (IRR, 0.71; 95% CI 0.53–0.95). Similar findings were reported from a large Canadian claims database  that examined adherence with a weekly dose (70 mg). After adjusting for potential confounding covariates, patients who were started on weekly buy MCC950 oral generic alendronate remained at a higher risk of early discontinuation compared to patients initiated
with weekly oral branded alendronate (IRR, 2.08; 95% CI 1.89–2.28) (Fig. 3). Fig. 3 Kaplan–Meier curves for the risk of early discontinuation during the year histone deacetylase activity following index date (first dispensation of bisphosphonate)  with kind permission from Springer Science + Business Media BV It might be argued that the introduction of generic alendronate resulted in a widening of the prescription market with the inclusion of patients less motivated to therapy and thus less compliant than formerly. This seems unlikely given that the same phenomenon was noted when patients established on treatment were switched from a branded to generic formulation. Following the introduction of generic alendronate to the Canadian market in July 2005, over 80% of patients were automatically switched from branded to generic alendronate without notification. An increase in the reports of adverse effects prompted a review of the case notes of 301 women with osteoporosis aged 50 years or more who had been established on treatment with alendronate 10 mg daily or 70 mg weekly between 2003 and 2007 . The rate of adverse events resulting in the discontinuation of treatment was significantly higher
after the introduction of generic alendronate than before (5.3/100 vs. 1.2/100 patient-years of exposure; PD184352 (CI-1040) p < 0.001). The majority of adverse events reported were upper gastrointestinal (61%). The higher rates of GI intolerance were associated with more frequent discontinuation of treatment and significant losses of bone mineral density (BMD) at the femoral neck and lumbar spine. A second retrospective chart review in Germany compared the effects of once weekly branded risedronate or alendronate with generic alendronate on BMD . Of 186 women with postmenopausal osteoporosis, treated for at least 12 months, there was a significantly higher incidence of gastrointestinal (and other) adverse events in women taking the generic drugs. Significantly smaller increments in BMD at the lumbar spine (p < 0.05) and total hip (p < 0.